To describe the epidemiology of VHFs To describe the public health action of VHFs To describe prevention and control procedures including employee health

1. Viral Hemorrhagic Fevers
Thein Shwe, MS, MPH
IDEP/DSDC/OEHP/WVBPH
September 25, 2003

2. Objectives
To describe the epidemiology of VHFs
To describe the public health action of
VHFs
To describe prevention and control
procedures including employee health

3. What are Viral Hemorrhagic
Fevers (VHFs)?
A group of illnesses that are caused by
several distinct families of viruses.
A severe multisystem syndrome (multiple
organ systems in the body are affected).
Vascular system damaged
Body’s ability to regulate itself is impaired.
Many cause severe and life-threatening
disease.

4. What are Viral Hemorrhagic
Fevers (VHF)? Cont.
Classified as biosafety level four (BSL4)
pathogens.
Classified as Category A Agent

5. How are VHF grouped?
4 distinct families
 Arenaviridae
 Filoviridae
 Bunyaviridae
 Flaviviridae

6. Hemorrhagic Fever Viruses
Hemorrhagic Fever Viruses
JAMA, 2002; 287:2391
Americas
Rodent
New World
Arenaviridae
Arenaviridae
West Africa
Rodent
Lassa
Hemorrhagic
Fever
Arenaviridae
Africa
Unknown
Marburg
Filoviridae
Africa
Unknown
Ebola
Filoviridae
Geographic
Distribution
Vector in
Nature
Disease
Family

7. Hemorrhagic Fever Viruses (2)
Hemorrhagic Fever Viruses (2)
JAMA, 2002; 287:2391
Asia Balkans,
Europe, Eurasia
Rodent
Hemorrhagic
Fever with Renal
Syndrome
Africa, Saudi
Arabia, Yemen
Mosquito
Rift Valley Fever
Africa, central
Asia, eastern
Europe, Middle
East
Tick
Crimean-Congo
Hemorrhagic
Fever
Bunyaviridae
Geographic
Distribution
Vector in
Nature
Disease
Family

8. Hemorrhagic Fever Viruses (3)
Hemorrhagic Fever Viruses (3)
JAMA, 2002; 287:2391
India
Tick
Kyasanur Forrest
Disease
Central Asia
Tick
Omsk Hemorrhagic
Fever
Africa, Tropical
Americas
Mosquito
Yellow Fever
Asia, Africa,
Pacific,
Americas
Mosquito
Dengue Fever,
Dengue hemorrhagic
fever, Dengue shock
syndrome
Flaviviridae
Geographic
Distribution
Vector in
Nature
Disease
Family

9. HFVs as potential biological
weapons
HFVs – weaponized by the Russia and
US
Yellow fever may have been weaponized
by North Korea
Source: JAMA, 2002; 287:2393

10. Epidemiology of HFVs
All RNA viruses, and all are covered, or
enveloped, in a fatty (lipid) coating
Survival depend on an animal or insect
host (the natural reservoir)
Geographically restricted to areas
where their host species live
Humans - not the natural reservoir but
are infected via contact with infected
hosts or arthropod vectors

11. Epidemiology of HFVs cont.
Naturally reside in an animal reservoir
host or arthropod vector
Rodents and arthropods – main
reservoirs for viruses causing VHFs.
Ticks and mosquitoes – vectors for
some VHFs
Ebola and Marburg – unknown host
factors

12. How are HFVs transmitted?
Exposure of urine, fecal matter, saliva, or
other body excretions from infected reservoir
hosts or vectors, e.g. rodents
Vector
From animals to humans
Person to person: e.g. Ebola, Marburg, Lassa
and Crimean-Congo hemorrhagic fever

13. Epidemiology of VHFs cont.
Source: JAMA, 2002; 287:2391
• No natural reservoir in West Virginia; consider:
– Travel
– BT
• Incubation period: 2 to 21 days
• Mortality: 0.5 to 90%

14. Arenaviridae
Classification:
 Old World and New World groups
 Life-long association with a rodent
reservoir
 Found in 1956 as Tacaribe virus (New
World virus) and discovered new
arenaviruses have been discovered every
one to three years

16. The Arenaviridae (Source: Chapter 29,
VHFs by Peter B Jahrling)
Arenavirus
Name
Disease Natural
Distribution
Source of
Human
Infection
Incubation
Period
(days)
Lassa Lassa Fever Africa Rodent
Nosocomial
5-16
Junin Argentine HF S. America Rodent
Nosocomial
7-14
Machupo Bolivian HF S. America Rodent
Nosocomial
9-15
Sabia Brazilian HF S America Rodent
Nosocomial
7-14
Guanarito Venezuelan
HF
South
America
Rodent
Nosocomial
7-14

17. Arenaviridae
Zoonotic
Rodents located in Europe, Asia, Africa,
and the Americas
Some Old World arenaviruses - rodent
population generation after generation
Some New World arenaviruses – transmitted
among adult rodents
Exception
 Tacaribe virus found in Trinidad – isolated from
a bat

18. Arenaviridae
The viruses - shed into the environment in the
urine or droppings of the infected hosts
Human infection – incidental –
 contact with excretions
 materials contaminated with the excretions of an
infected rodent
 ingestion of contaminated food,
 or by direct contact with broken skin with rodent
excrement
 Aerosol transmission (inhalation of tiny particles soiled
with rodent urine or saliva
 Agricultural work
 Human homes or other buildings – domestic settings

19. Arenaviridae
Lassa and Machupo viruses
 Associated with secondary person-to-
person and nosocomial (health-care
setting) transmission
 Contact with contaminated objects –
medical equipment

20. Filoviridae
Filovirus
 Marburg – 1967 in Marburg, Germany and
Yugoslavia
 Ebola – 1976 in Zaire and Sudan
 4 species identified – Ivory Coast, Sudan, Zaire, &
Reston
 18 reports of human outbreak due to Ebola or
Marburg viruses – approximately 1500 cases to
date
 Most in Africa
 Source of Human infection: Unknown
 Incubation Period – 3-16 days

21. Filoviridae
(Source: CDC)

22. Filoviridae
High mortality rate especially
percutaneous transmission
Transmission due to needle stick
injuries or use of contaminated syringes
Require low inocula for infection

23. Transmission by mucosal exposure in
experimental animals
Human infections – through contact of
contaminated fingers with oral mucosa
or conjunctiva
Person to person by small droplet
airborne nuclei
Filoviridae

24. Bunyaviridae
Bunyaviridae
Name
Disease Natural
Distribution
Source of
Human
Infection
Incubation
Period (days)
Phlebovirus Rift Valley
Fever
Africa Mosquito
Slaughter of
domestic
animal
2-5
Nairovirus Crimean-
Congo HF
Europe, Asia,
Africa
Tick
Slaughter of
domestic
animal,
nosocomial
3-12
Hantavirus Hemorrhagic
fever with
Renal
Syndrome
(HFRS)
Asia, Europe,
possibly
worldwide
Rodent 9-35

25. Flaviridae
Virus
Flaviviridae
Disease Natural
Distribution
Source of
Human
Infection
Incubation
Period (days)
Yellow Fever Yellow fever Tropical Africa,
South America
Mosquito 3-6
Dengue Dengue fever,
Dengue
hemorrhagic
fever, and
Dengue shock
syndrome
Asia,
Americas,
Africa
Mosquito Unknown for
dengue HF,
but 3-5 for
uncomplicated
dengue
Kyasanur
forest fever
Kyasanur
Forest disease
India Tick 3-8
Omsk HF Omsk
hemorrhagic
fever
Soviet Union Tick, Muskrat-
contaminated
water
3-8

26. Infectious Period
Viruses have been found in seminal
fluid of patients or sexually transmitted
as follows:
 Ebola – 82-101 days after symptom onset
 Marburg – 83 days
 Lassa – 90 days
 Junin – 7-22 days
 Lassa fever virus – in urine of patients 32
days after symptom onset

27. Clinical Manifestations of
VHFs
Nonspecific
May not be possible to differentiate by clinical
grounds alone
Overall incubation period: 2 –21 days
Initially – nonspecific prodrome lasts less
than a week
High fever, malaise, headache, arthralgias,
myalgias, nausea, abdominal pain, and
nonbloody diarrhea

28. Clinical Manifestations of VHFs
Filoviruses, Rift Valley fever, and flaviviruses :
characterized by an abrupt onset
Arenaviruses – more insidious onset
Early signs typically include
 Fever, hypotension, relative bradycardia,
tachypnea, conjunctivitis, and pharyngitis
 Cutaneous flushing or a skin rash
 Petechiae, mucous membrane and conjunctival
hemorrhage Hematuria, hematemesis, and
melena
 DIC and circulatory shock
 CNS dysfunction

29. Maculopapular Rash
Marburg Disease
(Source: JAMA; 287:2397)

30. Erythematous Rash
Bolivian Hemorrhagic Fever
(Source: JAMA; 287:2397)

31. Ocular Manifestation
Bolivian Hemorrhagic Fever
(Source: JAMA; 287:2397)

32. Clinical Characteristics of Hemorrhagic
Fever Viruses
Virus Distinctive Clinical Features Mortality, %
Ebola High fever, severe prostration, A diffuse
maculopapular rash by day 5, bleeding
and DIC common
50-90
Marburg High fever, myalgias, nonpruritic
maculopapular rash of the face, neck,
trunk, and arms may develop. Bleeding
and DIC common
23-70
(Source: JAMA, 2002; 287:2396)

33. Clinical Characteristics of Hemorrhagic Fever
Viruses
Lassa Fever Gradual onset of fever, nausea, abdominal pain,
severe sore throat, cough, conjunctivitis,
ulceration of buccal mucosa, exudative
pharyngitis, and cervical lymphadenopathy,
late signs: severe swelling of head and neck;
pleural and pericardial effusions, hemorrhagic
complication less common
15-20
Yellow Fever Fever, myalgias, facial flushing, and conjunctival
injection. Patients either recover or enter a short
remission followed by fever, relative bradycardia,
jaundice, renal failure, and hemorrhagic
complications
20
(Source: JAMA, 2002; 287:2396)

34. Clinical Characteristics of Hemorrhagic
Fever Viruses (Source: JAMA, 2002; 287:2396)
Virus Distinctive
Clinical Features
Mortality %
Rift Valley fever Fever, headache, retro-
orbital pain,
photophobia, and
jaundice. Less than 1%
develop hemorrhagic
fever or encephalitis.
Retinitis affects
approximately 10%,
which may occur at time
of acute febrile illness or
up to 4 weeks later
<1

35. Clinical Characteristics of Hemorrhagic Fever
Viruses
Virus Distinctive Clinical Features Mortality
%
Omsk
hemorrhagic
fever
Fever, cough, conjunctivitis, papulovesicular
eruption to the soft palate, marked
hyperemia of the face and trunk (but no
rash), generalized lymphadenopathy, and
splenomegaly. Pneumonia and CNS
dysfunction
0.5-10
Kyasanur
Forest
disease
Similar to Omsk but biphasic illness: first
phase lasts 6-11 days and is followed by an
afebrile period of 9-21 days. Up to 50% of
patients relapse and develop
meningoencephalitis
3-10
(Source: JAMA, 2002; 287:2396)

36. Case Definition / Confirmation
Suspect index case:
–Temperature > 101 of < 3 weeks duration
–No predisposing factors for hemorrhagic symptoms
–Two or more hemorrhagic symptoms:
•hemorrhagic or purple rash,
•Epistaxis (nosebleed),
•Hematemesis (vomiting of blood),
•Hemoptysis (spitting of blood derived from lung or airways),
•blood in stools,
•Other – conjunctival hemorrhage, bleeding gums, bleeding at puncture
sites, hematuria(blood in urine)
–No established alternative diagnosis
•Laboratory confirmation @ CDC / USAMRIID
JAMA, 2002; 287:2391

37. Differential Diagnosis of VHFs
Influenza
Viral hepatitis
Staphylococcal or
gram-negative sepsis
Toxic shock syndrome
Meningococcemia
Salmonellosis
Shigellosis
Rickettsial diseases
(e.g. Rocky Mountain
Spotted Fever)
Leptospirosis
Borreliosis
Psittacosis
Dengue
Hantavirus pulmonary
syndrome
Malaria
Trypanosomiasis
Septicemic plague
Rubella
Mealses
Hemorrhagic smallpox

38. Differential Diagnosis of VHFs cont.
Noninfectious bleeding diathesis
 Idiopathic or thrombotic thrombocytopenic
purpura
 Hemolytic uremic syndrome
 Acute leukemia
 Collagen-vascular diseases

39. Lab Abnormalities
Leukopenia (except in some cases of
Lassa fever – leukocytosis)
Anemia or hemoconcentration
Thrombocytopenia
Elevated liver enzymes

40. Jaundice – typical in Rift Valley fever and
yellow fever
Coagulation abnormalities – prolonged
bleeding time, prothrombin time, and
activated partial thromboplastin time
Elevated fibrin degradation products
Decreased fibrinogen
Urinalysis – proteinuria, and hematuria
Lab Abnormalities…cont.

41. Lab Testing for VHFs
Blood and serum specimens
Environmental samples should be taken
when possible and appropriate for exposure
assessment
Specimens should be sent to OLS which will
coordinate to submit to CDC
IgM ELISA, PCR, Viral Isolation, IgG ELISA
(recovered), Immunohistopathology testing
for deceased

42. Public Health Action
Protect employee health
 Identify high risk employees
 Educate high risk employees
 Personal Protective Equipment (PPE)
 Educate health care providers and the
public in the recognition and diagnosis of
VHF
 Educate providers and laboratories to
report VHF to the LHD immediately

43. Public Health Action cont.
When a VHF case is reported
 Isolation of case
 Confirm cases
 Obtain a complete clinical and lab history by using
VHF case investigation form
 Assure to obtain appropriate lab specimens on each
suspected case and send it to OLS
 Confirmation of an intentional or unintentional
exposure and notification procedure
 Checking for natural exposures to HFV, contact
of a case or travel to an endemic area within last
21 days
 If no clear source is identified, begin active
surveillance

44. Public Health Action cont.
Case Finding
 Develop a working case definition for the
outbreak investigation
 Begin enhanced passive surveillance
 Issue a news release and provide alert to
increase health care providers and the public
recognition and diagnosis of VHF
 Educate providers and lab to immediately
report possible VHF infections

45. Public Health Action cont.
Identify contact
Contact Definition
 Direct Contacts – any person who has had
face-to-face contact (within 6 feet) with a
suspected, probable, or confirmed case of
VHFs during the infectious period (onset of
symptoms until time of interview, recovery,
or death and burial of case).

46. Public Health Action cont.
Surveillance of case-contacts and
exposed population:
 Interview case-contacts and exposed
individuals: assure that all case-contacts
and exposed are contacted within 24 hours
and interview daily for 21 days after last
exposure.
 Determine if fever>101•F or VHF
symptoms
 Refer symptomatic persons to a clinical
center for isolation and treatment

47. Public Health Action cont.
Surveillance of exposed:
 If exposed does not have fever of 101 F
or higher or signs/symptoms of VHF by
end of 21 days – discontinue surveillance
 Interview all exposed individuals to verify
they have no symptoms – indicate status of
exposed individual as “closed” on Exposed
Individual Line Listing Form

48. Public Health Action cont.
If exposed have fever 101•F or higher,
or signs/symptoms of VHF, then assure
referral to a MD for diagnostic work-up
Implement appropriate infection control
and preventive interventions
Enter status of exposed individual as a
case and move to Case Line List Form
Begin contact tracing for this new case

49. Preventive Interventions:
Employee Health And Infection Control
•Hand hygiene; wash:
–Before donning protective equipment
–After removal of gown, leg and shoe covers, gloves
–Before removal of face and eye protection
•Double gloves
JAMA, 2002; 287:2391

50. Preventive Interventions:
Employee Health And Infection Control
Impermeable gowns
• Negative pressure isolation room
• N-95 masks or powered air-purifying respirators
• Leg and shoe coverings
• Goggles / face shields
• Restricted access of non-essential staff / visitors
• Dedicated medical equipment
• Environmental disinfection with 1:100 bleach
JAMA, 2002; 287:2391

51. Treatment and Prophylaxis
JAMA, 2002; 287:2391
•Prophylaxis: none
•Treatment: experimental use of ribavirin
–Arenaviridae
•Lassa hemorrhagic fever
–Bunyaviridae
–Rift Valley fever

52. Treatment Recommendation
The mainstay of treatment – supportive
 Fluid maintenance of fluid and electrolyte
balance, circulatory volume, and blood
pressure
 No antiviral drugs or vaccines
 If a case is suspected, probable or confirmed
the following drug therapy is recommended:
 Initial supportive and ribavirin therapy immediately
while diagnostic confirmation is pending
 If infection with Arenaviruses or Bunyaviruses is
confirmed, continue 10-day course of ribavirin
 If infection with Filovirus or Flavirus is confirmed, or
is the diagnosis of VHF is excluded or an alternative
diagnosis is established, discontinue ribavirin.
Source: JAMA, 2002; 287:2399